Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain

Neuropharmacology. 2006 Jun;50(8):941-52. doi: 10.1016/j.neuropharm.2006.01.005. Epub 2006 Mar 31.


Organic cation transporters (OCTs) are polyspecific carriers implicated in low-affinity, corticosteroid-sensitive extraneuronal catecholamine uptake in peripheral tissues. The three main OCT subtypes, OCT1, OCT2 and OCT3, are also present in the brain, but their central role remains unclear. In the present study, we investigated by comparative in situ hybridization analysis the regional distribution of these transporters in rat brain and compared their functional properties in stably transfected HEK293 cells expressing human or rat OCTs. In rat brain, OCT2 and OCT3 mRNAs are expressed predominantly in regions located at the brain-cerebrospinal fluid border, with OCT3 mRNA expression extending to regions that belong to monoaminergic pathways such as raphe nuclei, striatum and thalamus. After normalization with MPP+ uptake, OCT2 and OCT3 subtypes share a similar monoamine preference profile, with higher transport efficacies for epinephrine and histamine than for the other monoamines. Interestingly, a significant level of epinephrine transport, previously only shown for rOCT2, is achieved by most OCTs subtypes. Finally, another novel finding was that OCTs are sensitive to 3,4-methylenedioxymetamphetamine (MDMA), phencyclidine (PCP), MK-801 and ketamine. Altogether, all our results suggest a functional specialization of OCT subtypes, based both on their intrinsic properties and their differential regional expression pattern in the brain.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine / pharmacology
  • Animals
  • Biogenic Monoamines / pharmacokinetics
  • Brain / drug effects
  • Brain / metabolism*
  • Cell Line
  • Cocaine / pharmacology
  • Dopamine Uptake Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • Humans
  • In Situ Hybridization / methods
  • N-Methylaspartate / pharmacology
  • Organic Cation Transport Proteins / classification
  • Organic Cation Transport Proteins / genetics
  • Organic Cation Transport Proteins / metabolism*
  • Protein Binding / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Transfection / methods
  • Tritium / pharmacokinetics


  • Biogenic Monoamines
  • Dopamine Uptake Inhibitors
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Organic Cation Transport Proteins
  • RNA, Messenger
  • Tritium
  • N-Methylaspartate
  • Amphetamine
  • Cocaine